Abstract
INTRODUCTION: Premature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties of bone marrow CD146(+) mesenchymal stem cells (MSCs) and CD144(+) endothelial cells (ECs) were separately investigated in rats with POI. METHODS: POI rats were classified into control POI, POI + CD146(+) MSCs, and POI + CD144(+) ECs groups. Enriched CD146(+) MSCs and CD144(+) ECs were directly injected into ovarian tissue (15 × 10(4) cells/10 μL) in relevant groups. After 4 weeks, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E(2)) levels were measured in blood samples. Ovarian tissues were collected and subjected to Hematoxylin-Eosin and Masson's trichrome staining. The expression of angp-2, vegfr-2, smad-2, -4, -6, and tgf-β1 was studied using qRT-PCR analysis. Histopathological examination indicated an increased pattern of atretic follicles in the POI group related to the control rats (P<0.0001). RESULTS: Data indicated that injection of POI + CD146(+) MSCs and CD144(+) ECs in POI rats reduced atretic follicles and increased the number of normal follicles (P<0.01). Along with these changes, the content of blue-colored collagen fibers was diminished after cell transplantation. Besides, cell transplantation in POI rats had the potential to reduce increased FSH, and LH levels (P<0.05). In contrast, E2 content was increased in POI + CD146(+) MSCs and POI + CD144(+) ECs groups compared to control POI rats, indicating restoration of follicular function. CD144(+) (smad-2, and -4) and CD146(+) (smad-6) cells altered the activity of genes belonging TGF-β signaling pathway. Unlike POI + CD146(+) MSCs, aberrant angiogenesis properties were significantly down-regulated in POI + CD144(+) ECs related to the control POI group (P<0.05). CONCLUSION: The transplantation of bone marrow CD146(+) and CD144(+) cells can lead to the restoration of ovarian tissue function in POI rats via modulating different mechanisms associated with angiogenesis and fibrosis.